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Biomedical subjects

S Kuwata

Publications and source records attributed to S Kuwata.

At least 91 records · Page 5Linked to original sources

Conformational difference between diastereomers of Dnp-Val-Aib-Gly-Leu-pNA studied by x-ray crystal analyses.

In order to investigate the conformational change of the alpha-aminoisobutyric acid (Aib) containing peptide by the D/L replacement of an amino acid residue, single crystals of two diastereomers, Dnp-L-Val-Aib-Gly-L-Leu-pNA (L-L isomer) and Dnp-D-Val-Aib-Gly-L-Leu-pNA (D-L isomer), were prepared from aqueous methanol solutions as CH3OH and CH3OH.H2O solvates, respectively, and were analyzed by the x-ray diffraction method. Molecular conformation of L-L isomer adopts consecutive two different types of beta-turns, a type II' beta-turn bent at Aib-Gly, and a type III beta-turn bent at Gly-Leu, stabilized by two intramolecular (Leu)NH...O = C(Val) and (pNA)NH...O = C(Aib) hydrogen bonds. In contrast, these two intramolecular hydrogen bonds lead the D-L isomer to a distorted 3(10)-helix conformation consisting of consecutive two type-III beta-turn of Aib-Gly-Leu sequence. The most significant structural difference between these diastereomers is the mutual orientation between the Dnp and pNA chromophores. While the extensive stacking of both the chromophores is intramolecularly formed for the folded conformation of L-L isomer, they are oriented toward an opposite direction in the open conformation of D-L isomer and are intermolecularly stacked with each other. The large separation between these diastereomers observed in the chromatography is discussed in the relation with their conformational differences.

Amino Acid Sequence↗

A study of the association between schizophrenia and the dopamine D3 receptor gene.

A study of the genetic association between schizophrenia and a BalI polymorphism in exon 1 of the dopamine D3 (DRD3) gene, a candidate gene for schizophrenia, was conducted. The polymorphism was examined in 91 patients whose symptoms satisfied DSM-III-R for schizophrenia and 90 controls. There were no significant differences between the groups in allele frequencies or genotype counts. Contrary to a previous report, the patients were no more likely to be homozygous than controls. Moreover, no association with the presence of illness could be demonstrated when the patients were grouped according to sex, age of onset, history of admission to psychiatric institutions or positive family history.

Adult↗

No evidence for a point mutation at codon 713 and 717 of amyloid precursor protein gene in Japanese schizophrenics.

A point mutation at codon 717 of amyloid precursor protein (APP) gene has been demonstrated to play an important pathogenic role in some cases of familial Alzheimer's disease (FAD). Recently, a single case of chronic schizophrenia with a point mutation at codon 713 of APP gene which sits very close to the mutation in FAD was reported. We screened for these two kinds of mutations in 39 schizophrenic patients using polymerase chain reaction (PCR) and restriction enzyme technique. A mutation of codon 713 creates a MaeIII restriction site and that of codon 717 creates a BclI site. Enzyme digestion with amplified PCR product revealed no restriction site in all subjects. None of our subjects had either of these two kinds of mutations. Our findings support the hypothesis that the case of a mutation at codon 713 of APP gene is a natural non-pathogenic variant and, as well as a mutation at codon 717, has no relation with the genetic predisposition to schizophrenia.

Adult↗

Genotyping and association analysis of HLA-B61 in Japanese.

The distribution of HLA-B61-related alleles, B*4002-B*4006, was examined in the Japanese population by using PCR-SSO and PCR-RFLP methods. About half of the B61-positive individuals possessed B*4002 and the remaining half possessed B*4006. In addition, these two major B61 alleles were separately associated with different HLA-C alleles: B*4002 exhibited a strong linkage disequilibrium with Cw10, whereas B*4006 was strongly associated with C blank and DR9. Amino acid residues that contribute to the serologic epitopes of the B61 group and their relationships with other HLA-B locus antigens are discussed.

Alleles↗

Tomato necrosis and the 369 nucleotide Y satellite of cucumber mosaic virus: factors affecting satellite biological expression.

To determine which factors can affect biological expression of the Y satellite RNA of cucumber mosaic virus (CMV) in tomato, three laboratories collaboratively exchanged their natural satellite variants, the corresponding recombinant DNA clones and helper virus strains, as well as tomato varieties, on which different observations previously reported were based. The effects of these materials and the influence of temperature on symptom expression were systematically studied. The results show that in a standardized tomato bioassay at 24 degrees C, the Y satellite, when supported by either CMV-1 or CMV-Y, did not induce tomato necrosis in the Rutgers variety but elicited a slower necrotic response in the Best of All variety that was variably lethal, as compared to the faster inevitably lethal response induced by a prototype necrogenic D satellite variant in both tomato varieties. At higher temperatures (26.5 to 32 degrees C) an extremely fast-killing necrosis caused by CMV-Y itself was observed. The study demonstrates that in experiments on virus symptom modulation induced by CMV satellites, the nature of the helper virus, host plant varieties, as well as the environmental conditions should be precisely defined, and the effects of each parameter change determined separately.

Mosaic Viruses↗

Chronic neutropenia associated with C2 and C9 deficiency.

A Japanese male with a deficiency of the second and ninth components of complement associated with chronic idiopathic neutropenia is presented. In this case the second component of complement is totally deficient while the ninth component is approximately half that of normal control. Neutrophil granulocytes are constantly few, but this case shows no evidence of susceptibility to either viral or bacterial infections. His HLA type is different from that of Caucasians, suggesting that the genetic abnormality responsible for the complement deficiency of this Japanese case is different from that seen in Caucasian patients.

Adult↗

Patients with Graves' disease who developed insulin autoimmune syndrome (Hirata disease) possess HLA-Bw62/Cw4/DR4 carrying DRB1*0406.

The insulin autoimmune syndrome (IAS) is characterized by the following diagnostic criteria: severe spontaneous hypoglycemia without evidence of exogenous insulin administration, high levels of total serum immunoreactive insulin, and the presence of a high titer of antiinsulin antibody. Just before the onset of IAS, 13 of the 35 (37%) patients with IAS examined in this study had taken methimazole for the treatment of Graves' disease. To investigate the difference between the Graves' disease patients treated with methimazole who developed IAS and other IAS patients, HLA class II genes in both groups were analyzed by serological and DNA typing methods. All 13 patients with Graves' disease who developed IAS possessed a specific allelic combination, Bw62/Cw4/DR4 carrying DRB1*0406, whereas only 1 of 50 Graves' disease patients without IAS had Bw62/Cw4/DR4 (odds ratio, 891; P < 1 x 10(-10)) and carried not DRB1*0406 (odds ratio, 2727; P < 1 x 10(-10)), but DRB1*0405. Of the 22 IAS patients without Graves' disease, 13 had the combination Bw62/Cw4/DR4 carrying DRB1*0406 (odds ratio, 19.0; P < 0.07). Thus, it is highly likely that patients with Graves' disease develop IAS via treatment with methimazole when their Bw62/Cw4/DR4 carry DRB1*0406.

Adolescent↗

Shunt nephritis: efficacy of an antibiotic trial for clinical diagnosis.

Coagulase negative staphylococcus, a normal skin flora, is especially nosopoietic under shunt management, because coagulase negative staphylococcus sometimes forms a biofilm around itself at catheter tips in vivo, which shields the organism from the effects of antibiotics. But it is difficult to distinguish this pathogen from a possible confounding contamination of a blood culture. In this article, we report a case, and discuss how a patient with suspected shunt nephritis should be examined and treated. In addition, to further histological and prognostic interpretation, we review the previously reported cases of shunt nephritis in Japanese adults.

Adult↗

Strong association of insulin autoimmune syndrome with HLA-DR4.

Insulin autoimmune syndrome is characterised by spontaneous hypoglycaemia without evidence of exogenous insulin administration, a high serum concentration of total immunoreactive insulin, and the presence of insulin autoantibodies in high titre. HLA typing of 27 patients with insulin autoimmune syndrome showed that all had DR4, which was present in only 43% of 51 healthy controls (odds ratio 72.1, p less than 2 x 10(-6), and 19 (70%) of the patients were positive for the allelic combination, Cw4, Bw62, and DR4. Analysis of the nucleotide sequences of the DRB1, DQA1, and DQB1 genes showed that all the patients had DRB1*0406, DQA1*0301, and DQB1*0302, compared with only 14% of the controls (odds ratio 281, p less than 1 x 10(-10). We conclude that the development of insulin autoimmune syndrome is associated with a strong genetic predisposition.

Adult↗

Conformation of diastereomeric peptide sequences: structural analysis of Z-D-Val-Ac6c-Gly-L-Phe-OMe.

We have recently undertaken a systematic structural analysis of fully protected tetrapeptides containing at the N- and C-terminus either homo- or heterochiral amino acids, spaced by an achiral dipeptide segment. The interest for this class of peptides derives from the observation that, on reverse-phase (HPLC), the homo- and heterochiral sequences have a markedly different retention times. The diastereomeric sequences, namely Z-(L/D)-Val-X-Y-L-Phe-OMe (X = Sar, Gly, Ac3c, Aib, Ac5c, Ac6c, Deg, Dpg, Dbu, Dip, Dph; Y = Sar, Gly, Ac3c, Aib, Ac5c, Ac6c) show different overall hydrophobicity attributed to a different three-dimensional structure that also depends on the X-Y segment. Therefore, following preliminary studies in solution, we report here the detailed x-ray analysis of the tetrapeptide Z-D-Val-Ac6c-Gly-L-Phe-OMe in order to understand the structural features governing the overall hydrophobicity of linear fully protected tetrapeptides.

Amino Acid Sequence↗

Structure of the L (polymerase) protein gene of sonchus yellow net virus.

The complete nucleotide sequence of the L protein gene of sonchus yellow net virus (SYNV), a plant rhabdovirus, was determined by dideoxynucleotide sequencing of cloned cDNAs derived from the negative-strand genomic RNA. The L protein gene is composed of 6401 nucleotides (nt) located between positions 7158 and 13558 relative to the 3' end of the genomic RNA. Sequence analysis suggests that the complementary mRNA contains a 44 nt untranslated 5' leader sequence preceding an open reading frame of 6348 nucleotides that is capable of encoding a polypeptide of 2116 amino acids with a deduced molecular weight of 241,569 Da. The L protein is positively charged, has a high proportion of the amino acids Leu and Ile, and contains putative polymerase and RNA binding domains. Extended alignment of the SYNV L protein amino acid sequence with those of other nonsegmented negative-strand RNA virus polymerases reveals conservation of sequences within 12 blocks that appear sequentially along the protein. A cluster dendrogram derived from the L protein alignments indicates that SYNV is more closely related to animal rhabdoviruses than to the paramyxoviruses and that the animal rhabdoviruses have diverged less from each other than from SYNV.

Amino Acid Sequence↗

Family study on HLA-DPB1 polymorphism: linkage analysis with HLA-DR/DQ and two "new" alleles.

An extensive family study on HLA-DPB1 was performed in 105 families living in northeastern Japan. In a linkage study between HLA-DPB1 and other HLA loci, five apparent recombinations between DPB1 and DR/DQ loci were observed. The recombination frequency (theta) with maximum probability was estimated to be 0.017 by the lod score method. DPB1 allele and haplotype frequencies in unrelated parents were determined by direct counting. The most common allele was DPB1*0501 with the frequency of 41.2% and the second was DPB1*0201 with 24.0%. Nine DPB1-DR and six DPB1-DQ haplotypes were in significant linkage disequilibrium. Seven kinds of extended haplotypes were observed to be over 1%, in which the most common haplotype A24-B52-DR15-DQ6-DPB1*0901 occurred at 6.0%. Moreover, we found two "new" DPB1 alleles in this study. The first one possesses a single base substitution from DPB1*0501 resulting in an amino acid change. The other is most likely to be formed by an intraexonic recombination between DPB1*0301 and DPB1*0501.

Alleles↗